Association between serum branched chain amino acids, mammalian target of rapamycin levels and the risk of gestational diabetes mellitus: a 1:1 matched case control study.
Branched chain amino acids
Gestational diabetes mellitus
Glucose tolerance
Mammalian target of rapamycin
Pregnancy
Journal
BMC pregnancy and childbirth
ISSN: 1471-2393
Titre abrégé: BMC Pregnancy Childbirth
Pays: England
ID NLM: 100967799
Informations de publication
Date de publication:
02 Oct 2024
02 Oct 2024
Historique:
received:
17
04
2023
accepted:
10
09
2024
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
2
10
2024
Statut:
epublish
Résumé
To investigate the association between serum branched chain amino acids (BCAAs), mammalian target of rapamycin (mTOR) levels and the risk of gestational diabetes mellitus (GDM) in pregnant women. 1:1 matched case-control study was conducted including 66 GDM patients and 66 matched healthy pregnant women (± 3 years) in 2019, in China. Fasting bloods of pregnant women were collected in pregnancy at 24 ~ 28 weeks gestation. And the serum levels of valine (Val), leucine (Leu), isoleucine (Ile) and mTOR were determined. Conditional logistic regressions models were used to estimate the associations of BCAAs and mTOR concentrations with the risk of GDM. Concentrations of serum Val and mTOR in cases were significantly higher than that in controls (P < 0.05). After adjusted for the confounded factors, both the second tertile and the third tertile of mTOR increased the risk of GDM (OR = 11.771, 95%CI: 3.949-35.083; OR = 4.869 95%CI: 1.742-13.611, respectively) compared to the first tertile of mTOR. However, the second tertile of serum Val (OR = 0.377, 95%CI:0.149-0.954) and the second tertile of serum Leu (OR = 0.322, 95%CI: 0.129-0.811) decreased the risk of GDM compared to the first tertile of serum Val and Leu, respectively. The restricted cubic spline indicated a significant nonlinear association between the serum levels of mTOR and the risk of GDM (P values for non-linearity = 0.0058). We confirmed the association of higher mTOR with the increased risk of GDM in pregnant women. Pregnant women who were in the certain range level of Val and Leu were at lower risk of GDM. Our findings provided epidemiological evidence for the relation of serum BCAAs and mTOR with risk of GDM.
Sections du résumé
BACKGROUND
BACKGROUND
To investigate the association between serum branched chain amino acids (BCAAs), mammalian target of rapamycin (mTOR) levels and the risk of gestational diabetes mellitus (GDM) in pregnant women.
METHODS
METHODS
1:1 matched case-control study was conducted including 66 GDM patients and 66 matched healthy pregnant women (± 3 years) in 2019, in China. Fasting bloods of pregnant women were collected in pregnancy at 24 ~ 28 weeks gestation. And the serum levels of valine (Val), leucine (Leu), isoleucine (Ile) and mTOR were determined. Conditional logistic regressions models were used to estimate the associations of BCAAs and mTOR concentrations with the risk of GDM.
RESULTS
RESULTS
Concentrations of serum Val and mTOR in cases were significantly higher than that in controls (P < 0.05). After adjusted for the confounded factors, both the second tertile and the third tertile of mTOR increased the risk of GDM (OR = 11.771, 95%CI: 3.949-35.083; OR = 4.869 95%CI: 1.742-13.611, respectively) compared to the first tertile of mTOR. However, the second tertile of serum Val (OR = 0.377, 95%CI:0.149-0.954) and the second tertile of serum Leu (OR = 0.322, 95%CI: 0.129-0.811) decreased the risk of GDM compared to the first tertile of serum Val and Leu, respectively. The restricted cubic spline indicated a significant nonlinear association between the serum levels of mTOR and the risk of GDM (P values for non-linearity = 0.0058).
CONCLUSION
CONCLUSIONS
We confirmed the association of higher mTOR with the increased risk of GDM in pregnant women. Pregnant women who were in the certain range level of Val and Leu were at lower risk of GDM. Our findings provided epidemiological evidence for the relation of serum BCAAs and mTOR with risk of GDM.
Identifiants
pubmed: 39358711
doi: 10.1186/s12884-024-06815-2
pii: 10.1186/s12884-024-06815-2
doi:
Substances chimiques
TOR Serine-Threonine Kinases
EC 2.7.11.1
Amino Acids, Branched-Chain
0
MTOR protein, human
EC 2.7.1.1
Leucine
GMW67QNF9C
Isoleucine
04Y7590D77
Valine
HG18B9YRS7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
633Informations de copyright
© 2024. The Author(s).
Références
Kim C. Gestational diabetes: risks, management, and treatment options. Int J Womens Health. 2010;2:339–51.
doi: 10.2147/IJWH.S13333
pubmed: 21151681
pmcid: 2990903
Nezami N, Safa J, Eftekhar-Sadat AT, Salari B, Ghorashi S, Sakhaee K, et al. Lovastatin raises serum osteoprotegerin level in people with type 2 diabetic nephropathy. Clin Biochem. 2010;43:1294–9.
doi: 10.1016/j.clinbiochem.2010.08.012
pubmed: 20727867
Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by international association of diabetes in pregnancy study group’s criteria. Diabetes Res Clin Pract. 2022;183: 109050.
doi: 10.1016/j.diabres.2021.109050
pubmed: 34883186
Zhang Q, Cheng Y, He M, Li T, Ma Z, Cheng H. Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: A randomized controlled trial. Exp Ther Med. 2016;12:1889–95.
doi: 10.3892/etm.2016.3515
pubmed: 27588106
pmcid: 4998009
Aittasalo M, Raitanen J, Kinnunen TI, Ojala K, Kolu P, Luoto R. Is intensive counseling in maternity care feasible and effective in promoting physical activity among women at risk for gestational diabetes? Secondary analysis of a cluster randomized NELLI study in Finland. Int J Behav Nutr Phys Act. 2012;9: 104.
doi: 10.1186/1479-5868-9-104
pubmed: 22950716
pmcid: 3511276
Xin G, Du J, Wang YT, Liang TT. Effect of oxidative stress on heme oxygenase-1 expression in patients with gestational diabetes mellitus. Exp Ther Med. 2014;7:478–82.
doi: 10.3892/etm.2013.1435
pubmed: 24396429
Noctor E, Crowe C, Carmody LA, Kirwan B, O’Dea A, Glynn LG, et al. ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria. Acta Diabetol. 2015;52:153–60.
doi: 10.1007/s00592-014-0621-z
pubmed: 25002067
Yong HY, Mohd Shariff Z, Mohd Yusof BN, Rejali Z, Appannah G, Bindels J, et al. The association between dietary patterns before and in early pregnancy and the risk of gestational diabetes mellitus (GDM): Data from the Malaysian SECOST cohort. PLoS One. 2020;15: e0227246.
doi: 10.1371/journal.pone.0227246
pubmed: 31923230
pmcid: 6953856
Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9:311–26.
doi: 10.1016/j.cmet.2009.02.002
pubmed: 19356713
pmcid: 3640280
Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. PLoS One. 2010;5: e15234.
doi: 10.1371/journal.pone.0015234
pubmed: 21170321
pmcid: 3000813
Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17:448–53.
doi: 10.1038/nm.2307
pubmed: 21423183
pmcid: 3126616
Chorell E, Hall UA, Gustavsson C, Berntorp K, Puhkala J, Luoto R, et al. Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes. Metabolism. 2017;72:27–36.
doi: 10.1016/j.metabol.2016.12.018
pubmed: 28641781
Park S, Park JY, Lee JH, Kim SH. Plasma levels of lysine, tyrosine, and valine during pregnancy are independent risk factors of insulin resistance and gestational diabetes. Metab Syndr Relat Disord. 2015;13:64–70.
doi: 10.1089/met.2014.0113
pubmed: 25419905
Bentley-Lewis R, Huynh J, Xiong G, Lee H, Wenger J, Clish C, et al. Metabolomic profiling in the prediction of gestational diabetes mellitus. Diabetologia. 2015;58:1329–32.
doi: 10.1007/s00125-015-3553-4
pubmed: 25748329
pmcid: 4428592
Shimobayashi M, Hall MN. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol. 2014;15:155–62.
doi: 10.1038/nrm3757
pubmed: 24556838
Dimasuay KG, Boeuf P, Powell TL, Jansson T. Placental responses to changes in the maternal environment determine fetal growth. Front Physiol. 2016;7:12.
doi: 10.3389/fphys.2016.00012
pubmed: 26858656
pmcid: 4731498
Muralimanoharan S, Maloyan A, Myatt L. Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: role of miR-143. Clin Sci (Lond). 2016;130:931–41.
doi: 10.1042/CS20160076
pubmed: 26993250
Hung TH, Wu CP, Chen SF. Differential changes in Akt and AMPK phosphorylation regulating mTOR activity in the placentas of pregnancies complicated by fetal growth restriction and gestational diabetes mellitus with large-for-gestational age infants. Front Med (Lausanne). 2021;8: 788969.
doi: 10.3389/fmed.2021.788969
pubmed: 34938752
Zhang Y, Liang Y, Liu H, Huang Y, Li H, Chen B. Paeoniflorin attenuates gestational diabetes via Akt/mTOR pathway in a rat model. Food Nutr Res. 2020;64:4362.
Capobianco E, Gomez Ribot D, Fornes D, Powell TL, Levieux C, Jansson T, et al. Diet Enriched with olive oil attenuates placental dysfunction in rats with gestational diabetes induced by intrauterine programming. Mol Nutr Food Res. 2018;62:e1800263.
doi: 10.1002/mnfr.201800263
pubmed: 29939470
Li G, Lin L, Wang YL, Yang H. 1,25(OH)2D3 protects trophoblasts against insulin resistance and inflammation via suppressing mTOR signaling. Reprod Sci. 2019;26:223–32.
doi: 10.1177/1933719118766253
pubmed: 29575997
Andersson-Hall U, Gustavsson C, Pedersen A, Malmodin D, Joelsson L, Holmäng A. Higher concentrations of BCAAs and 3-HIB are associated with insulin resistance in the transition from gestational diabetes to type 2 diabetes. J Diabetes Res. 2018;2018:4207067.
doi: 10.1155/2018/4207067
pubmed: 29967793
pmcid: 6008749
Allalou A, Nalla A, Prentice KJ, Liu Y, Zhang M, Dai FF, et al. A predictive metabolic signature for the transition from gestational diabetes mellitus to type 2 diabetes. Diabetes. 2016;65:2529–39.
doi: 10.2337/db15-1720
pubmed: 27338739
pmcid: 5001181
Rahimi N, Razi F, Nasli-Esfahani E, Qorbani M, Shirzad N, Larijani B. Amino acid profiling in the gestational diabetes mellitus. J Diabetes Metab Disord. 2017;16:13.
doi: 10.1186/s40200-016-0283-1
pubmed: 28367428
pmcid: 5374565
Li N, Li J, Wang H, Liu J, Li W, Yang K, et al. Branched-chain amino acids and their interactions with lipid metabolites for increased risk of gestational diabetes. J Clin Endocrinol Metab. 2022;107:e3058–65.
doi: 10.1210/clinem/dgac141
pubmed: 35271718
pmcid: 9891107
Zhao L, Wang M, Li J, Bi Y, Li M, Yang J. Association of circulating branched-chain amino acids with gestational diabetes mellitus: a meta-analysis. Int J Endocrinol Metab. 2019;17: e85413.
doi: 10.5812/ijem.85413
pubmed: 31497040
pmcid: 6679587
Pappa KI, Vlachos G, Theodora M, Roubelaki M, Angelidou K, Antsaklis A. Intermediate metabolism in association with the amino acid profile during the third trimester of normal pregnancy and diet-controlled gestational diabetes. Am J Obstet Gynecol. 2007;196(65):e61-65.
Shang M, Wen Z. Increased placental IGF-1/mTOR activity in macrosomia born to women with gestational diabetes. Diabetes Res Clin Pract. 2018;146:211–9.
doi: 10.1016/j.diabres.2018.10.017
pubmed: 30389621
Tsai K, Tullis B, Jensen T, Graff T, Reynolds P, Arroyo J. Differential expression of mTOR related molecules in the placenta from gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia patients. Reprod Biol. 2021;21: 100503.
doi: 10.1016/j.repbio.2021.100503
pubmed: 33826986
Xu K, Bian D, Hao L, Huang F, Xu M, Qin J, et al. microRNA-503 contribute to pancreatic beta cell dysfunction by targeting the mTOR pathway in gestational diabetes mellitus. Excli J. 2017;16:1177–87.
pubmed: 29285014
pmcid: 5735340
Wen J, Bai X. miR-520h Inhibits cell survival by targeting mTOR in gestational diabetes mellitus. Acta Biochim Pol. 2021;68:65–70.
pubmed: 33620957
Kalhan SC. Protein metabolism in pregnancy. Am J Clin Nutr. 2000;71:1249s–55s.
doi: 10.1093/ajcn/71.5.1249s
pubmed: 10799398
Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. 2016;351:43–8.
doi: 10.1126/science.aab2674
pubmed: 26449471
Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, et al. Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice. Metabolism. 2014;63:841–50.
doi: 10.1016/j.metabol.2014.03.006
pubmed: 24684822
Bridi R, Braun CA, Zorzi GK, Wannmacher CM, Wajner M, Lissi EG, et al. alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats. Metab Brain Dis. 2005;20:155–67.
doi: 10.1007/s11011-005-4152-8
pubmed: 15938133
Funchal C, Latini A, Jacques-Silva MC, Dos Santos AQ, Buzin L, Gottfried C, et al. Morphological alterations and induction of oxidative stress in glial cells caused by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. Neurochem Int. 2006;49:640–50.
doi: 10.1016/j.neuint.2006.05.007
pubmed: 16822590